Dysfunction of CNS regulatory processes has been proposed to contribute to the development and maintenance of central sensitization in patients with persistent musculoskeletal pain. Psychophysical findings have suggested abnormalities in three such processes: the touch gate (inhibition of mechanoreception by pain), diffuse noxious inhibitory control (DNIC, inhibition of pain by pain) and the pain gate (inhibition of pain by mechanoreception). However, few human neuroimaging investigations have attempted to study these processes in either normal subjects or patients. To this end, this project will study the direct and indirect effects of these regulatory processes on the cortical response to non-painful tactile and painful thermal stimuli with high-resolution electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). The extents will be determined (i) to which concurrent noxious thermal stimulation of skin alters the cortical response to vibrotactile stimuli (touch gate), (ii) to which the effects of the noxious thermal stimulation are further altered by tonic, counter-irritant stimulation of muscle (DNIC), and (iii) to which vibrotactile stimulation alters the cortical response to the experimentally induced pain (pain gate). As in Subprojects by Maixner and Hollins, the regulatory mechanisms will be studied in two populations of patients whose sensory abnormalities suggest abnormal central sensitization: patients diagnosed with fibromyalgia (FM) and with myogenous temporomandibular disorders (TMD). The findings will contribute to an understanding of differences in the operation of CNS regulatory systems in healthy individuals and patients with persistent musculoskeletal pain. The findings will help identify specific neurophysiological concomitants of central sensitization and CNS regulatory effects studied in depth psychophysically in Subprojects by Maixner and Hollins.